UK Boy with SDS Headed to Transplant

This is a newspaper article about a boy in the UK who is headed for bone marrow transplant.  Kane Prepares for Transplant

Targeted Radiotherapy for BMT - clinical trial

http://www.virtualmedicalcentre.com/news.asp?artid=13100&title=World-first-as-myeloma-patient-in-new-clinical-trial-is-given-targeted-radiotherapy-treatment

World first as myeloma patient in new clinical trial is given targeted radiotherapy treatment
21 Jan 2009

A patient from the Isle of Wight with the blood cancer multiple myeloma has become the first person in the world to receive a new form of radiotherapy which targets cancer cells without damaging healthy organs. In a clinical trial funded by Leukaemia Research, Pauline Pain has received a much higher dose of radioactivity delivered accurately to the bone marrow than would otherwise have been possible.
High doses of radioactivity are needed to completely eradicate cancer cells in the bone marrow. This cannot be risked with standard treatments such as total body irradiation, which cause “collateral damage” to healthy tissues, specifically the liver, and may be fatal. The new treatment uses a radioactive isotope attached to an antibody that specifically targets a protein present on myeloma tumour cells in the bone marrow.
Pauline Pain, age 58, from the Isle of Wight is the first person to be treated in the clinical trial, which is assessing the effect of the new radiotherapy treatment on patients with myeloma – an as yet incurable bone marrow cancer that causes extensive bone damage and a failure of the bone marrow to make healthy blood cells.
Following the new targeted radiotherapy treatment, Pauline was able to return home to await her bone marrow transplant (BMT). Conventional total body irradiation would have meant a long stay in hospital.
Pauline says: “The only side-effects of the radiotherapy were a little temporary tiredness and mild sickness; other than that I felt very, very well. It was incredible to be walking around knowing that something inside me was fighting the cancer, but I couldn’t feel it at all”.
Dr Kim Orchard, senior lecturer in the University of Southampton’s School of Medicine, who is leading the trial at Southampton General Hospital explains: "Radiotherapy is used to clear the bone marrow of myeloma cells before a stem cell transplant. Current treatment uses high doses of radiation, which are delivered by X-rays but the sensitivity of healthy organs limits the dose that can be tolerated. “
“Previous attempts to use antibodies to deliver the radioactivity have been frustrated by their accumulation in the liver, lungs and kidneys, which can cause serious complications and may be fatal. The key to this promising new treatment is that the antibody only accumulates in the bone marrow and not in other tissues.”
The new type of radiotherapy works by delivering the radio-isotope Yttrium-90 attached to an antibody which targets a protein called CD-66, found on the surface of bone marrow cells and myeloma tumour cells. The radioactive Yttrium-90 delivers radiation specifically to sites of disease in the bone marrow and as a result, destroys the bone marrow and any tumour cells. This is followed by a transplant of healthy stem cells collected from the patient at an earlier time.
Dr Orchard said: “The early results using this new approach to bone marrow transplantation are very encouraging with high doses of radiation targeted to the bone marrow without any side-effects. We are currently using the targeted radiation in addition to chemotherapy and we hope that the trial will show a clear benefit in better and longer remissions from myeloma. If we are successful, then this approach offers great promise for the treatment of patients who need a bone marrow transplant for a range of other blood cancers such as leukaemia.”
Dr David Grant, Scientific Consultant at Leukaemia Research, said: “This trial is very exciting. One of the main reasons why stem cell transplants have been less successful in the long-term treatment of myeloma is that patients are not cleared of all the cancer cells before the transplant. This new radiotherapy is not only more effective and potentially cheaper than existing treatments, it is far less toxic for the patient. It also enables patients to go home immediately after the procedure, reducing time spent in hospital.”
(Source: Leukaemia Research: January 2009)



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Camp notes: BMT

I wrote down a few things he said that were not on his slides…… just thought I’d share for those interested.

There are 7-8 million people in registry (US) and there are more in Europe. (This is up from the stats in 2006!!! Interesting)

He has a bit on the slides about the regimen…but not with numbers—he said they used this regimen on 50 patients in Cinci (I believe they were all Fanconi’s patients who have the same toxicity issues as SDSers) and they have used it on the 7 SDSers he reports on the slides.

The aplastic anemia patients did better than the MDS and Leukemia patients. The one adult with Leukemia is currently going through transplant again there in Cinci.

The regimen in Cinci begins 3 weeks before transplant—they start the Campath then. (this is on the slides)

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Camp notes Dr. S BMT talk/Suggested monitoring of bone marrow failurees:

Dr. S and Dr. H both gave talks on BMT topics. Dr. H had handouts and I don’t think Dr. S did—she did get her hematology 101 or hematology basics handouts to us….. these are my notes from her talks…. If she had hand outs and I missed them….could someone send me a copy?



Here are my notes from her talk on BMT:



One of the questions she had up on the board was: when should transplant be considered?



Donor selection



First choice: HLA matched sibling who does not have SDS.
Be sure to check CBC for siblings. This is particularly difficult in patients without SBDS mutations. This is important! Must look for even subtle changes in CBC or marrow in sibling donors.


Basic principles of HSCT

Cytoreduction (conditioning)
immunosuppression (prevent graft rejection)
myeloablation (make room for new stem cells)
anti leukemic effect (kill minimal residual disease)


Conditioning—this is done by using chemotherapy with or without radiation (TBI) (TBI= total body irradiation)


Acute complications of allogeneic SCT

Immunologic
Endocrine issues are particularly important for children
Increased risk of solid tumors


Reduced Intensity Regimens

Advantage: reduced toxicity of conditioning regimen
Potential problems: not myeloablative (at least not in non-SDS patients)so there is a theoretical risk that premalignant host marrow cells might persist. It might actually be sufficient, but marrow might have SDS marrow left so SDS cells left could cause problems (Dr. Harris addressed this in his talk—not on his handouts--)


Timing of transplant

Factors increasing transplant associated risks
active or occult infections
organ dysfunction
leukemia (need to identify patients at high risk for leukemia)
Age: as patients get older, more side effects/transplant related risks increase
Risk of “preemptive transplant”

Cannot predict whether any individual patient will eventually need a transplant


Transplant planning

HLA matching—get plans in place—it can take up to 6 months to find a donor.
If you have a rare HLA type—start early


Suggested Clinical Monitoring of Bone Marrow Failure

If blood counts are stable (in the normal/mildly low range)and clonal cytogenetics are absent: blood counts every 3-4 months and Bone marrow with cytogenetics every year
Clinical management if new cytogenetic clone is detected or blood counts are falling or rising: counts every 1-2 months, BMB with cytogenetics, then every one-six months, have plans for possible transplant in place. If everything then remains stable, may be able to back off of such frequent monitoring, but the clinical course will determine this.


Dr. S felt that it is important to use a study protocol so that they can learn from the experience. There in Seattle, they are using a new protocol called protocol 2256 using Treosulfan. Treosulfan has been used in SDS patients in Europe. The contact for the Seattle (she flashed this fast) is : lburrough@fhcrc.org


For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

New Booklet Available

Shwachman-Diamond America is pleased to announce that we have a new booklet available. The title is Management of the Hematologic Abnormalities of Shwachman-Diamond Syndrome by Richard Harris, M.D. This booklet is excellent for parents, pediatricians and specialists. If you would like a copy (or copies) of the booklet sent to you, please send your mailing address to shwachmandiamondamerica@embarqmail.com These booklets are FREE to anyone who requests them. Visit the webstie above to request your free booklet.

The booklet includes sections on the following topics:

Description
History
Diagnosis
Management of Neutropenia
Management of Fevers in SDS patients
Antibiotic coverage prior to Dental Work or Surgical Procedures
Management of other Cytopenias
Management of Anemia during Surgical Procedures
Management of MDS
Management of Leukemia
Bone Marrow Transplantation for SDS
And also includes the following:
K-M Survival Plots
Important Contacts
References
Glossary
All of us at Shwachman-Diamond America would like to take this opportunity to thank Dr. Harris for all of his hard work and dedication to this project. Thank you, Dr. Harris, from the bottom of our hearts! Your dedication to all of our SDS and SDS-like children is appreciated more than you will ever know.


For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Reduced-intensity conditioning is effective and safe for transplantation of patients with Shwachman-Diamond syndrome.

Bone Marrow Transplant. 2008 May 26.

Reduced-intensity conditioning is effective and safe for transplantation of patients with Shwachman-Diamond syndrome.
Bhatla D, Davies SM, Shenoy S, Harris RE, Crockett M, Shoultz L, Smolarek T, Bleesing J, Hansen M, Jodele S, Jordan M, Filipovich AH, Mehta PA.

[1] 1Department of Hematology Oncology, Cincinnati Children's Hospital and Medical Center, Cincinnati, OH, USA [2] 2Division of Hematology Oncology, Cardinal Glennon Children's Medical Center, St Louis, MO, USA.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only potentially curative treatment for the BM dysfunction seen in patients with Shwachman-Diamond syndrome (SDS). Historically, these patients have fared poorly with intensive conditioning regimens with increased regimen-related toxicity especially involving the heart and lungs. We report our institutional experience with a reduced-intensity-conditioning protocol in seven patients with SDS and BM aplasia or myelodysplastic syndrome/AML. The preparative regimen consisted of Campath-1H, fludarabine and melphalan. Four patients received matched related marrow and three received unrelated stem cells (two PBSCs and one marrow). All but one was 8 of 8 allele HLA matched. All patients established 100% donor-derived hematopoiesis. No patient in this cohort developed grades III-IV GVHD. One patient had grade II skin GVHD that responded to systemic corticosteroids and one had grade I skin GVHD, treated with topical corticosteroids. Two out of seven patients developed bacterial infections in the early post transplant period. Viral infections were seen in four out of seven patients and were successfully treated with appropriate antiviral therapy. All patients are currently alive. These data indicate that HSCT with reduced-intensity conditioning is feasible in patients with SDS and associated with excellent donor cell engraftment and modest morbidity.Bone Marrow Transplantation advance online publication, 26 May 2008; doi:10.1038/bmt.2008.151.


For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America